title: Fisetin protects against hepatosteatosis in mice by inhibiting miR-378.
abstract: METHODS
  Lipid homeostasis in vertebrates is regulated at many levels including synthesis, degradation, and distribution. MicroRNAs (miRNAs) are key regulators of lipid homeostasis. The use of phytochemicals to target miRNA (miR) could provide new therapeutic approaches to human diseases. Thus, we investigated the regulation of lipid metabolism by the flavonoid fisetin during experimental analysis of hepatic miRs in mice.
  
  
  RESULTS
  Mice were separated into three groups. One group was maintained on the normal diet and the other two groups were fed either a high-fat (HF) diet or HF supplemented with fisetin. We found that fisetin lowered hepatic fat accumulation in HF mice and reversed abnormal expressions of lipid metabolism genes. The co-expression of miR-378 and its host gene PGC-1β was significantly induced by HF, whereas fisetin prevented the induction of both genes. We also identified nuclear respiratory factor-1 (NRF-1), a critical regulator of the mitochondrial function, as a direct target of miR-378.
  
  
  CONCLUSIONS
  Dietary fisetin protects against hepatosteatosis in association with modulation of lipid metabolism genes and miR-378 in mice. These observations suggest that the use of fisetin to target miRs could be an effective prevention or intervention against metabolic diseases.
authors.affiliation: Department of Animal Science, College of Agriculture and Life Science, Chonnam National University, Gwangju, Korea; Division of Metabolism and Functionality Research, Korea Food Research Institute, Seoungnam, Korea.
authors.forename: Tae-Il
authors.initials: TI
authors.lastname: Jeon
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Jiyun
authors.initials: J
authors.lastname: Ahn
authors.forename: Chang Hwa
authors.initials: CH
authors.lastname: Jung
authors.forename: Tae Youl
authors.initials: TY
authors.lastname: Ha
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control*; D005419:Flavonoids / Q000008:administration & dosage*; D044948:Flavonols; D005786:Gene Expression Regulation; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000517:prevention & control*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005419:Flavonoids; D044948:Flavonols; C546119:MIRN378 microRNA, mouse; D035683:MicroRNAs; C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D014280:Triglycerides; D012313:RNA; C017875:fisetin
keywords: Fisetin; Hepatosteatosis; Lipid homeostasis; microRNA